Exercise + Liraglutide for Metabolic Syndrome

(ZQL008 Trial)

Overseen By Linda Jahn, MEd

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Virginia

Must not be taking: Diabetes medications, Liraglutide

Disqualifiers: Diabetes, Smoking, Hypertriglyceridemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how exercise, a medication called liraglutide (an injection), or a combination of both can aid people with metabolic syndrome. Metabolic syndrome includes conditions that raise the risk of heart disease, such as a large waist, high blood pressure, and high blood sugar. Participants will join one of four groups: exercise alone, liraglutide alone, both treatments, or no treatment, for 24 weeks. This trial suits individuals who meet specific health criteria and have not been exercising regularly or using liraglutide before. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Do I need to stop my current medications for the trial?

You can continue taking certain medications if the doses have been stable for at least 3 months. These include medications like ACE inhibitors, ARBs, statins, and others listed in the trial criteria.

What is the safety track record for these treatments?

Previous studies have shown that exercise is safe and effective for people with metabolic syndrome. It typically improves fitness and blood sugar control without major side effects.

Liraglutide, another treatment studied, is generally well-tolerated. Research shows it aids in weight loss and enhances metabolism. Some individuals might experience mild side effects, such as nausea, but these are usually manageable.

When combined, exercise and liraglutide further reduce weight and improve health markers. Previous research indicates this combination is safe. Overall, both treatments are considered safe options for improving metabolic health. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they explore the combined effects of exercise and Liraglutide on metabolic syndrome. Unlike standard treatments that typically focus on medication or lifestyle changes alone, this approach integrates both. Liraglutide is a medication that mimics a hormone that helps control blood sugar and appetite, potentially offering more comprehensive management of metabolic syndrome. The exercise component adds a physical activity dimension, which is known to improve heart health and insulin sensitivity. Together, these treatments could offer a more holistic and effective way to tackle the condition compared to traditional options.

What evidence suggests that this trial's treatments could be effective for Metabolic Syndrome?

Studies have shown that exercise can improve body shape, heart health, and metabolism in people with metabolic syndrome. Combining aerobic exercises (like walking or cycling) with resistance training (like lifting weights) yields the best results for these health issues. In this trial, some participants will receive exercise alone as a treatment. Liraglutide, another treatment option in this trial, has effectively helped people lose weight and manage metabolic syndrome. Research shows that about 61.5% of patients using liraglutide lost at least 5% of their body weight. Another group of participants will receive liraglutide alone. Combining exercise with liraglutide, another arm of this trial, can further reduce the severity of metabolic syndrome, aiding in weight loss and lowering inflammation. These treatments have proven effective both individually and together. ^{1 6 7 8 9}

Who Is on the Research Team?

Zhenqi Liu, MD

Principal Investigator

Division of Endocrinology and Metabolism, University of Virginia

Are You a Good Fit for This Trial?

Adults aged 21-60 with Metabolic Syndrome, not currently very active, and have a stable weight (BMI between 25-35) can join. They must meet at least three criteria like large waist size, high triglycerides or blood sugar, low HDL cholesterol, or high blood pressure. Those on certain stable medications may also qualify.

Inclusion Criteria

I meet at least 3 of the 5 criteria for Metabolic Syndrome.

I am between 21 and 60 years old.

Your "good" cholesterol (HDL) is too low.

Exclusion Criteria

I have diabetes or have taken medication for it.

You have been regularly doing intense exercise for at least 20 minutes, two times a week.

You have very high levels of triglycerides or cholesterol in your blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of four groups: control, exercise training, liraglutide treatment, or exercise + liraglutide for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise training
• Liraglutide

Trial Overview The study is testing the effects of exercise alone, the drug Liraglutide alone, and both combined on heart and muscle blood flow and insulin function in people with Metabolic Syndrome over 24 weeks. Participants will be randomly placed into one of four groups including a control group.

How Is the Trial Designed?

Group I: Liraglutide Alone Experimental Treatment 1 Intervention

24 weeks of treatment

Group II: Exercise Alone Experimental Treatment 1 Intervention

24 weeks of treatment

Group III: Exercise + Liraglutide Experimental Treatment 1 Intervention

24 weeks f treatment

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Exercise training significantly improves insulin sensitivity, glucose tolerance, and lowers triglyceride and cholesterol levels in nondiabetic, nonobese individuals with hypertriglyceridemia, but these benefits are not observed in patients with impaired glucose tolerance.

In severely obese individuals without diabetes, combining exercise with a calorie-restricted diet enhances insulin sensitivity, while in obese patients with non-insulin dependent diabetes, adding exercise to sulfonylurea therapy improves insulin sensitivity and reduces glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus. Lampman, RM., Schteingart, DE.[2007]

Supervised, long-term moderate to moderately vigorous exercise training can significantly improve lipid profiles in overweight and obese adults with metabolic syndrome, even without weight loss, by increasing HDL cholesterol and decreasing triglycerides.

Lifestyle changes, including exercise and dietary modifications, are crucial for improving insulin resistance and glucose tolerance, and they play a key role in preventing or delaying type 2 diabetes in individuals at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome. Carroll, S., Dudfield, M.[2022]

Liraglutide is an effective treatment for type 2 diabetes, reducing hemoglobin A1c levels by 0.8% to 1.5%, and is safe for patients at risk of hypoglycemia due to its low incidence of this side effect.

It is particularly beneficial for overweight or obese patients, as it not only helps control blood sugar but also promotes weight loss of about 2%-4% of initial body weight, although nausea can occur but is typically manageable with careful dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pearls for initiating and utilizing liraglutide in patients with type 2 diabetes. Gross, B.[2015]

Regular exercise can significantly improve glycemic control and reduce risk factors for coronary heart disease in individuals with type II diabetes, particularly by enhancing insulin sensitivity.

There is a notable lack of research on the effects of exercise specifically in Black individuals with type II diabetes, despite their higher prevalence of the condition and associated cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in therapy and prevention of type II diabetes. Implications for blacks. Ruderman, N., Apelian, AZ., Schneider, SH.[2022]

Liraglutide is an effective treatment for type 2 diabetes, showing greater improvement in glycemic control compared to other incretin-based therapies, with sustained benefits observed over a period of up to 2 years.

The medication is generally well tolerated, with a low risk of hypoglycemia and mild to moderate gastrointestinal side effects that decrease with continued use, while also offering additional benefits like weight reduction and improved beta-cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide in type 2 diabetes mellitus. Baruah, MP., Chaudhury, T., Sethi, BK., et al.[2018]

Structured endurance exercise can significantly improve glycemic control, insulin sensitivity, and cardiovascular risk factors in individuals with Type 2 diabetes, showing effects comparable to standard medications.

While exercise is beneficial, adherence to structured programs can be challenging, and more research is needed to understand the impact of lifestyle-based physical activity and the specific types and amounts of exercise that are most effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting the role of physical activity and exercise in the treatment of type 2 diabetes. Tudor-Locke, CE., Bell, RC., Meyers, AM.[2019]

In diabetics, the metabolic response to exercise is influenced by insulin availability, with acute exercise lowering blood glucose in insulin-dependent patients but potentially increasing it in insulin-deficient, ketotic patients.

Regular exercise improves insulin sensitivity and positively affects lipid metabolism, which may benefit diabetic patients by enhancing their overall metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in diabetes: therapeutic implications. Koivisto, VA., Sherwin, RS.[2019]

Increased daily physical activity can prevent type 2 diabetes and help treat metabolic syndrome, showing effects on glycaemic control comparable to oral antidiabetic medications.

Exercise, whether endurance or strength training, improves insulin resistance and body composition, and when combined with a proper diet, can also help correct issues like dyslipidaemia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical training in the treatment of metabolic syndrome]. Dela, F.[2017]

Regular physical activity leads to significant metabolic and cardiovascular adaptations that can improve insulin resistance, which is crucial for managing metabolic syndrome.

Patient motivation and adherence to exercise therapy are essential for achieving positive treatment outcomes in individuals with metabolic syndrome, highlighting the need for a comprehensive approach to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Exercise therapy for patients with metabolic syndrome]. Svacinová, H.[2017]

Insulin resistance and hyperinsulinemia are key features of metabolic syndrome, which can lead to serious health issues like type 2 diabetes and cardiovascular disease, but regular exercise and calorie restriction can improve insulin sensitivity.

The review highlights that AMP-activated protein kinase (AMPK) plays a crucial role in regulating insulin sensitivity and may be a promising target for preventing and treating metabolic syndrome-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPK, insulin resistance, and the metabolic syndrome. Ruderman, NB., Carling, D., Prentki, M., et al.[2022]

Liraglutide, now available at a higher dose of 3.0 mg for treating obesity, has been shown to effectively control appetite and promote weight loss when combined with diet and exercise, based on results from the SCALE studies.

The drug is already established for managing type 2 diabetes at lower doses, and its mechanism of action includes effects on the endocrine pancreas and appetite regulation in the hypothalamus, indicating a dual benefit for patients with obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY]. Scheen, AJ.[2016]

Liraglutide, approved for Type 2 diabetes and chronic weight management, works by increasing insulin secretion and decreasing appetite, which helps promote weight loss.

Recent findings suggest that liraglutide may also protect against prediabetes and prevent bone loss by enhancing bone formation after weight loss, highlighting its broader health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide for Type 2 diabetes and obesity: a 2015 update. Iepsen, EW., Torekov, SS., Holst, JJ.[2015]

Liraglutide (Saxenda) has been shown to effectively promote weight loss in overweight and obese patients, with a higher percentage achieving 5% and 10% weight loss compared to placebo and orlistat, based on randomized controlled studies.

The medication is generally safe, with gastrointestinal side effects being the most common and typically dose-dependent, making it a viable adjunct to lifestyle changes for obesity management, especially in patients with prediabetes and women with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide: an injectable option for the management of obesity. Clements, JN., Shealy, KM.[2022]

Citations

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Effectiveness of Physical Exercise on Indicators of Metabolic ... Furthermore, substantial evidence suggests that resistance-trained muscle may lead to greater improvements in glucose regulation compared to ...

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Physical activity in metabolic syndrome - PMC Aerobic training (AT) is the most effective type of exercise in health problems as-sociated with MetS. A study by Bateman et al. (2011) found that AT improved ...

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Effects of amount, intensity, and mode of exercise training ... Combined aerobic and resistance training interventions offer the most robust improvements for composite MetS outcomes compared to either mode alone.

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The effects of combined exercise training on glucose ... Another study also observed that 12 weeks of combined training in obese adults with metabolic syndrome improved fasting glucose, insulin, HOMA- ...

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Physical activity in metabolic syndrome Early implementation of exercise leads to improved physical fitness, better glycemic control and lipid profile. Undertaking systematic PA is associated with ...

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Effects of concurrent continuous aerobic and short rest ... This study aimed to systematically evaluate the impact of a 12-week concurrent training program combining continuous aerobic exercise and short- ...

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Physical Activity, Cardiorespiratory Fitness, and the ... Those in the lifestyle intervention group (aerobic exercise 150 minutes per week and nutritional counseling) achieved a 38% reversal of the metabolic syndrome ...